Concomitant Chronic Heart Failure Research Articles

Low irisin levels predict acutely decompensated heart failure in type 2 diabetes mellitus patients

Abstract Funding Acknowledgements None. Background Acutely decompensated heart failure (ADHF) continues to be associated with unacceptably increasing in-hospital mortality rates and one-year mortality rates. Distinct scenarios of the natural course of ADHF relate to clinical heterogeneity among patients admitted to hospitals, cardiac dysfunction etiology, precipitating factors contributing to heart failure (HF) decompensation including type 2 diabetes mellitus (T2DM). The aim of this study was to determine the discriminative value of irisin for ADHF in T2DM patients with hemodynamically stable chronic HF. Methods A total of 738 patients with T2DM were prescreened using the local database of "Vita Center" (Ukraine). Using criteria of inclusion (male/female with age of ≥18 years, established T2DM with hemodynamically stable chronic HF, glycosylated hemoglobin < 6.9%, informed consent to participate in the study), we enrolled 489 patients with T2DM with concomitant chronic HF I-IV New York Heart Association (NYHA) functional classes. We enrolled 480 T2DM patients with any phenotype of HF and followed them for 52 weeks. Hemodynamic performances and the serum levels of biomarkers were detected at the study entry. The primary clinical end-point was ADHF that led to urgent hospitalization. Results We found that the serum levels of N-terminal natriuretic pro-peptide (NT-proBNP) were higher (1719 [980-2457] pmol/mL vs. 1057 [570-2607] pmol/mL, respectively) and the levels of irisin were lower (4.96 [3.14-6.85] ng/mL vs. 7.95 [5.73-9.16] ng/mL) in ADHF patients than in those without ADHF. The ROC curve analysis showed that the estimated cut-off point for serum irisin levels (ADHF versus non-ADHF) was 7.85 ng/mL (area under curve [AUC] = 0.869 (95% CI = 0.800-0.937), sensitivity = 82.7%, specificity = 73.5%; p = 0.0001). The multivariate logistic regression yielded that the serum levels of irisin < 7.85 ng/mL (OR = 1.20; p = 0.001) and NT-proBNP > 1215 pmol/mL (OR = 1.18; p = 0.001) retained the predictors for ADHF. Kaplan-Meier plots (Figure) showed a significant difference of clinical end-point accumulations in patients with HF depending on irisin levels (<7.85 ng/mL versus ≥7.85 ng/mL). The intra-class correlation coefficient for inter-observer reproducibility of LV dimensions was 0.88 (95% CI = 0.83–0.92), of LVEF was 0.93 (95% CI = 0.90–0.97), of LAVI was 0.92 (95% CI = 0.89–0.94), and of E/e’ was 0.90 (95% CI = 0.87–0.94). Along with it, the intra-class correlation coefficient for the intra-observer reproducibility of LV dimensions was 0.91 (95% CI = 0.88–0.95), of LVEF was 0.94 (95% CI = 0.90–0.98), of LAVI was 0.95 (95% CI = 0.93–0.97), and of E/e’ was 0.92 (95% CI = 0.90–0.95). In conclusion, we established that decreased levels of irisin were associated with ADHF presentation in chronic HF patients with T2DM independently from NT-proBNP.Flow chart of the study designThe Kaplan–Meier analysis of ADHF

PREDICTORS OF KIDNEY EVENTS IN TYPE 2 DIABETES MELLITUS PATIENTS WITH CHRONIC HEART FAILURE PATIENTS

Objective: Sodium-glucose cotransporter 2 inhibitors (SGLT2i) have a favorable impact on the kidney function in patients with heart failure (HF), while there is no clear evidence of what factors predict this effect. The aim of the study was to identify plausible predictors for kidney function outcome among patients with HF and investigate their association with SGLT2i. Design and method: We prospectively enrolled 480 patients with type 2 diabetes mellitus (T2DM) treated with diet and metformin and concomitant chronic HF and followed them for 52 weeks. We determined kidney outcome as a composite event that includes >40% reduced estimated glomerular filtration rate from baseline, newly diagnosed end-stage CKD or kidney replacement therapy. The relevant medical information and measurement of the biomarkers were collected at baseline and at the end of the study. Results: The composite kidney outcome was detected in 88 (18.3%) patients of the entire population. All patients received guideline-recommended optimal therapy, which was adjusted to phenotype/severity of HF, cardiovascular risk and comorbidity profiles, and fasting glycaemia. Levels of irisin, adropin and apelin significantly increased in patients without clinical endpoint, whereas in those with composite endpoint the biomarker levels exhibited a decrease with borderline statistical significance (Figure 1). Multivariate logistic regression revealed that use of SGLT2i (OR=0.92 p=0.048), baseline serum levels of irisin <4.50 ng/ml (OR=1.51, p=0.001) and adropin <2.10 ng/ml (OR=1.15, p=0.001) along with and a <15% increase in the levels of these biomarkers (OR=1.60, p=0.001)and <6% (OR=1.21, p=0.001), respectively, remained an independent predictor for composite kidney endpoint. We established that irisin <4.5 ng/ml and <15% increase in irisin serum levels added more valuable predictive information than the reference variable. However, the combination of irisin <4.5 ng/ml at baseline and <15% increase in irisin serum levels (area under curve = 0.91, 95% confident interval = 0.87-0.95) improved the discriminative value of each biomarker alone. Conclusions: We suggest that low levels of irisin and its inadequate increase during administration of SGLT2i are promising predictors for unfavorable kidney outcome among patients with T2DM and concomitant HF

Results of the DAPA-CKD trial and their impact on clinical practice

Chronic kidney disease (CKD) is a growing medical and social problem in the world. Data from population base stu­dies demonstrate an increase in the prevalence of CKD and mortality. One of the causes is an increase in the number of patients with diabetes. Another reason is the limited ability to prevent the progression of the loss of kidney function. The first studies with dapagliflozin, such as DECLARE-TIMI 58 in patients with type 2 diabetes, showed a slowing of the progression of CKD to end-stage renal disease. The DAPA-CKD trial included patients with both type 2 diabetes and those without diabetes with an estimated glomerular filtration rate of 25 to 75 ml/min/1.73 m2 and albuminuria. The DAPA-CKD trial was terminated prematurely by independent monitors because of dapagliflozin overwhelming placebo. The primary endpoint, which included a sustained decrease in estimated glomerular filtration rate ≥ 50 %, end-stage renal disease, or death from renal or cardiovascular causes, was 39 % lower in the dapagliflozin group than in the placebo group. The effect of dapagliflozin on the primary endpoint was also similar among patients with dia­betic nephropathy, glomerulonephritis, ischemic or hypertensive CKD, and CKD of other or unknown cause. Also, the effect of dapagliflozin was the same regardless of concomitant cardiovascular diseases or chronic heart failure. All-cause mortality was 31 % lower among patients who received dapagliflozin at a dose of 10 mg. Dapagliflozin also significantly reduced the frequency of sudden decline in kidney function in CKD patients by 32 %. According to the results of a post-hoc analysis of the DAPA-CKD trial, compared to placebo, dapagliflozin reduced the frequency of hospitalizations due to cardiac causes, kidney and urinary tract diseases, metabolic and nutritional disorders, and oncological problems. This effect of dapagliflozin was independent of baseline type 2 diabetes. Based on the DAPA-CKD trial, dapagliflozin was approved by the Food and Drug Administration for use in reducing the risk of worsening kidney function, kidney failure, cardiovascular death, and heart failure hospitalization in adults with CKD.

Progressive right ventricular dysfunction and exercise impairment in patients with heart failure and diabetes mellitus: insights from the T.O.S.CA. Registry

BackgroundFindings from the T.O.S.CA. Registry recently reported that patients with concomitant chronic heart failure (CHF) and impairment of insulin axis (either insulin resistance—IR or diabetes mellitus—T2D) display increased morbidity and mortality. However, little information is available on the relative impact of IR and T2D on cardiac structure and function, cardiopulmonary performance, and their longitudinal changes in CHF.MethodsPatients enrolled in the T.O.S.CA. Registry performed echocardiography and cardiopulmonary exercise test at baseline and at a patient-average follow-up of 36 months. Patients were divided into three groups based on the degree of insulin impairment: euglycemic without IR (EU), euglycemic with IR (IR), and T2D.ResultsCompared with EU and IR, T2D was associated with increased filling pressures (E/e′ratio: 15.9 ± 8.9, 12.0 ± 6.5, and 14.5 ± 8.1 respectively, p < 0.01) and worse right ventricular(RV)-arterial uncoupling (RVAUC) (TAPSE/PASP ratio 0.52 ± 0.2, 0.6 ± 0.3, and 0.6 ± 0.3 in T2D, EU and IR, respectively, p < 0.05). Likewise, impairment in peak oxygen consumption (peak VO2) in TD2 vs EU and IR patients was recorded (respectively, 15.8 ± 3.8 ml/Kg/min, 18.4 ± 4.3 ml/Kg/min and 16.5 ± 4.3 ml/Kg/min, p < 0.003). Longitudinal data demonstrated higher deterioration of RVAUC, RV dimension, and peak VO2 in the T2D group (+ 13% increase in RV dimension, − 21% decline in TAPSE/PAPS ratio and − 20% decrease in peak VO2).ConclusionThe higher risk of death and CV hospitalizations exhibited by HF-T2D patients in the T.O.S.CA. Registry is associated with progressive RV ventricular dysfunction and exercise impairment when compared to euglycemic CHF patients, supporting the pivotal importance of hyperglycaemia and right chambers in HF prognosis.Trial registration ClinicalTrials.gov identifier: NCT023358017

Cardiac biomarkers on admission and in‑hospital mortality in COVID-19 patients with or without concomitant heart failure.

High‑sensitivity cardiac troponin T (hs-cTnT) and N-terminal pro-B type natriuretic peptide (NT‑ proBNP) are known markers of cardiac injury. However, their role in predicting the severity of COVID‑19 remains to be investigated. We aimed to analyze the association between hs‑cTnT and NT-proBNP levels and in hospital mortality in patients with COVID‑19, with emphasis on those with concomitant chronic heart failure (CHF). A total of 1729 consecutive patients with COVID‑19 were enrolled. Demographic data, laboratory parameters, and clinical outcomes (discharge or death) were analyzed. Receiver operating characteristic (ROC) and logistic regression analyses were performed to evaluate the association between hs‑cTnT and NT-proBNP values and the risk of death. Evaluation of hs‑cTnT was performed in 1041 patients, while NT-proBNP was assessed in 715 individuals. CHF was present in 179 cases (10.4% of the cohort). Median values of hs‑cTnT and NT-proBNP and in‑hospital mortality were higher in CHF patients than in those without CHF. Among patients without CHF, mortality was the highest in those with hs‑cTnT or NT-proBNP values in the fourth quartile. In ROC analysis, hs‑cTnT equal to or above 142 ng/l and NT-proBNP equal to or above 969 pg/ml predicted in‑hospital death. In patients without CHF, each 10-ng/l increase in hs-cTnT or 100-pg/ml increase in NT‑proBNP was associated with a higher risk of death (odds ratio [OR], 1.01 and OR, 1.02, respectively; P <0.01 for both). The level of hs‑cTnT or NT-proBNP predicts in hospital mortality in COVID-19 patients. Both hs‑cTnT and NT-proBNP should be routinely measured on admission in all patients hospitalized due to COVID‑19 for early detection of individuals with an increased risk of in hospital death, even if they do not have concomitant heart failure.

Peculiarities of pharmacotherapy of chronic heart failure with retained left ventricular efficiency and associated atrial fibrilation depending on the method of heart rhythm control

Introduction. Only small studies in selected centers have examined the effect of rhythm control strategy, including catheter ablation, on major cardiovascular events, mortality in patients with long-term atrial fibrillation and concomitant chronic heart failure with preserved left ventricular ejection fraction and features of pharmacotherapy. The aim. To study the peculiarities of pharmacotherapy in patients with heart failure with preserved left ventricular ejection fraction and concomitant atrial fibrillation over a long period of observation, depending on the implementation of a rhythm control strategy: radiofrequency ablation or pharmacotherapy and their impact on endpoints. Materials and Methods. The study included 194 patients with a mean age of 59.3 ± 8.5 years with atrial fibrillation and concomitant heart failure with preserved left ventricular ejection fraction I–III of the NYHA functional class. Patients were divided into 2 groups: 136 patients who underwent radiofrequency ablation, and 58 patients in the control group who did not undergo intervention and continued antiarrhythmic pharmacotherapy. The patients were compared according to the main clinical and demographic indicators. An assessment was made of the characteristics of pharmacotherapy and different stages of observation by group and its impact on endpoints. Results. In the control group, the use of antiarrhythmic drugs other than amiodarone and oral anticoagulants at the baseline of the study was associated with the primary endpoint. The chance of its occurrence was 3.9 times higher among patients taking other antiarrhythmic drugs (odds ratio–3.949, 95 % confidence interval 1.198–13.013) and 1.8 times lower among patients taking anticoagulants (odds ratio - 0.556, 95 % confidence interval 0.399–0.965). In the ablation group, the chance of a primary endpoint event occurring was 3.1 times higher among patients taking diuretics at 2-year follow-up (odds ratio –3.130, 95 % confidence interval 1.111–8.824), and beta-blockers were associated with 3.4 times lower chance of these events (odds ratio – 0.296, 95 % confidence interval 0.128–0.688). In the ablation group, there was a statistically significant decrease in the percentage of patients requiring diuretics 2 years after inclusion in the study compared with the 3-month stage (p &lt; 0.001) and the inclusion stage (p &lt; 0.001). Conclusions. Long-term use of beta-blockers after intervention is associated with a reduced risk of primary endpoint events in the ablation group. Taking diuretics, beta-adrenergic receptors, and renin-angiotensin-aldosterone system inhibitors during the first 3 months after the intervention reduces the risk of atrial fibrillation recurrence in the long-term follow-up period in the ablation group.

Treatment strategies for patients with atrial fibrillation and chronic heart failure

Atrial fibrillation (AF) is associated with significant morbidity and mortality and may lead to the development of chronic heart failure (CHF). Each condition predisposes to the other, requiring a careful choice of the treatment strategy. This article is devoted to the prevalence and prognostic implications of both diseases. The article presents data from meta-analyzes related to the management of this group of patients. The aspects of rhythm control strategy in AF and concomitant CHF are described according to the recent studies and clinical guidelines. The features of anticoagulant therapy in patients with AF and CHF are outlined. Much attention is given to the importance of the safety profile of the anticoagulant therapy in terms of the bleeding risk in patients with concomitant AF and CHF.

Biomarker Value in the Diagnosis of Community-Acquired Pneumonia with Concomitant Chronic Heart Failure.

The diagnosis of community-acquired pneumonia (CAP) with chronic heart failure (CHF) is associated with objective difficulties. Our case–control study aims to establish whether established serum inflammatory biomarkers are relevant to the diagnosis of CAP in patients with CHF. Seventy inpatients with previously diagnosed CHF and suspected non-severe CAP were recruited and then stratified into two subgroups with confirmed and rejected diagnosis of CAP. C-reactive protein (CRP), procalcitonin (PCT), tumor necrosis factor α (TNFα), interleukin-6 (IL-6) and brain natriuretic peptide (BNP) were measured. The value of biomarkers was determined using logistic regression, and their discriminatory efficacy was assessed by analyzing receiver operating characteristic (ROC) curves. Significantly higher levels of CRP 50.0 (35.5–98.5) mg/L, PCT 0.10 (0.05–0.54) ng/mL and IL-6 46.1(21.4–150.3) pg/mL in cases were identified as compared to the control group—15.0 (9.5–25.0) mg/L, 0.05 (0.05–0.05) ng/mL and 13.6 (9.5; 25.0) pg/mL, respectively. The Area Under the ROC Curve (95% CI) was the highest for CRP—0.91 (0.83–0.98), followed by PCT—0.81 (0.72–0.90) and IL-6—0.81 (0.71–0.91). A CRP value of >28.5 mg/L had an optimal sensitivity and specificity ratio (85.7/91.4%). In conclusion, the measurement of serum CRP, PCT and IL-6 levels can be useful for the diagnosis of CAP in patients with CHF. CRP showed optimal diagnostic utility in this population.

FEATURES OF CLINICAL AND STRUCTURAL AND FUNCTIONAL HEART CHANGES IN PATIENTS WITH AH ACCORDING TO TISSUE DOPPLEROGRAPHY DATA

Arterial hypertension (AH) remains one of the most important causes of chronic heart failure (CHF). In recent years, close attention has been paid to the study of indicators of tissue Doppler ultrasonography, as early markers of the development of CHF [A. Lerman, 1993; M. Davis, 1994; European guidelines for the diagnosis and treatment of CHF, 2005]. In hypertension, the study of tissue Doppler imaging parameters can serve as a reliable marker of diastolic heart failure. At the same time, tissue Doppler data are extremely important for assessing the prognosis in hypertension, especially in concomitant CHF.

Outcomes and predictors of hospital mortality of patients with Philadelphia-negative myeloproliferative neoplasms and sepsis: A Nationwide Inpatient Sample Database analysis.

e19038 Background: Sepsis is associated with increased mortality in patients with hematologic malignancies, especially in those receiving cytotoxic chemotherapy. The development of new therapies also increases the risk of infections in Philadelphia negative myeloproliferative neoplasms (MPN). However, the clinical implications and costs of sepsis in patients with polycythemia vera (PV), essential thrombocytosis (ET), and primary myelofibrosis (PMF) have not been reported at a national level. Therefore, we aimed to determine the outcomes, hospitalization costs, and predictors of mortality in patients with MPN and sepsis. Methods: We retrieved adult patients with MPN from the Nationwide Inpatient Sample database from 2016-2018. We used the ICD-10 codes to identify and compare patients with and without sepsis. The main outcomes were hospital mortality and predictors of mortality. We computed the chi-squared test and the Mann-Whitney U-test. Mortality predictors are estimated using multivariate logistic regression and logistic fixed-effect methods to control for admission cohort and hospital time invariant characteristics. All analyses were performed using Stata Statistical Software version 14 (StataCorp, College Station, TX). Results: A total of 86,723 patients with MPN were identified. The majority of them were white (66.9%), female (54.3%), with a median age of 62 (IQR 47-76). The most common MPN was ET (84.3%), followed by PV (14.2%). Sepsis was diagnosed in 16,146 (18.6%) of the MPN patients. There was a significantly higher mortality in the sepsis group vs. the non-sepsis group (7.4% vs. 1.8%; p &lt; 0.001), longer LOS (8 vs. 4 days; p &lt; 0.001), and higher median hospitalization cost (US$74,128 vs. US$39,987; p &lt; 0.001). In the multivariable analysis, sepsis was associated with higher mortality (OR: 4.74; CI 95%: 4.33-5.18; p &lt; 0.001). Among the MPN, those with PMF and sepsis had a higher risk of death (OR: 2.21; CI 95%: 1.72-2.82; p &lt; 0.001). Other significant variables associated with mortality were age &gt; 65 (OR: 2.51; CI 95%: 2.14-2.95; p &lt; 0.001), concomitant chronic heart failure (CHF) (OR: 1.57; CI 95%: 1.39-1.77; p &lt; 0.001), chronic kidney disease (CKD) (OR: 1.22; CI 95%: 1.10-1.35; p &lt; 0.001), and weight loss (OR: 2.12; CI 95%: 1.79-2.51; p &lt; 0.001). There was no significant association with sex and race/ethinicity. Conclusions: On patients with MPN, sepsis was associated with higher mortality, hospitalization costs, and LOS. Additionally, those with increased age, CHF, CKD, weight loss, and PMF were also at increased risk of death. There should be more emphasis on assessing the risk of sepsis on MPN to prevent worse outcomes and higher costs. Further studies should focus on identifying the specific causes of sepsis in MPN and promoting early recognition.

Clinical and financial implications of central venous catheters bloodstream infections in patients with multiple myeloma in the United States.

e20033 Background: Multiple Myeloma(MM) has an increased exposure to intravascular catheters due to the increased risk of severe infections and due to the route of treatment administration. Central Venous Catheter Bloodstream Infections(CVCBI) have significant mortality, imply a delay in treatment and increased cost as well. There is no prior report on the risk factors for poor outcome in MM patients that develop this complication. We aim to describe the predictors of mortality as well as the changes in cost that CVCBI implies. Methods: We retrieved adult patients with MM from the Nationwide Inpatient Sample database from 2016-2018. We used the ICD-10 codes to identify and compare patients who developed CVCBI with those that did not developed it. The main outcomes were hospital mortality and predictors of mortality. We computed the chi-squared test and the Mann-Whitney U-test. Mortality predictors are estimated using multivariate logistic regression and logistic fixed-effect methods to control for admission cohort and hospital time invariant characteristics. All analyses were performed using Stata Statistical Software version 14 (StataCorp, College Station, TX). Results: A total of 58,838 patients with MM were identified. The majority were white (63.5%), male (55.3%), with a median age of 70 (IQR 62-78). Most MM were not in remission (99.1%), followed by those in remission (1.3%) and relapse (0.3%). CVCBI was diagnosed in 264 (0.4%) of the MM patients. There was significantly higher mortality in the CVCBI group vs. the non-CVCBI group (8.7% vs. 5%; p &lt; 0.01), longer LOS (10 vs. 5 days; p &lt; 0.001), and higher median hospitalization cost (US$86,168 vs. US$43,511; p &lt; 0.001). In the multivariable analysis, CVCBI was associated with higher mortality (OR: 1.69; CI 95%: 1.14-2.52; p &lt; 0.001). Among patients with MM and CVCBI those that had achieved remission had a higher risk of death (OR: 2.87; CI 95%: 2.17-3.8; p &lt; 0.001). Other variables associated with mortality were age &gt; 65 (OR: 1.84; CI 95%: 1.59-2.15; p &lt; 0.001), concomitant chronic heart failure (CHF) (OR: 1.46; CI 95%: 1.29-1.65; p &lt; 0.001), chronic kidney disease (CKD) (OR: 1.43; CI 95%: 1.32-1.56; p &lt; 0.001), and weight loss (OR: 2.31; CI 95%: 1.91-2.8; p &lt; 0.001). When compared to medicare patients with higher mortality were more likely to be under medicaid(OR: 1.25; CI 95%: 1.02-1.55; p &lt; 0.05) and private insurances(OR: 1.31; CI 95%: 1.15-1.49; p &lt; 0.001). There was no significant association with sex, race/ethinicity or household income. Conclusions: In patients with Multiple Myeloma the development of Central Venous Catheter Bloodstream Infections was associated with a higher overall mortality, length of stay and cost of hospitalization. Age, CHF, CKD and weight loss were independent risk factors for poor outcome in this patient population. Further studies are required on developing strategies for the prevention of this complication.

Synergistic effects of ivabradine and metformin in the treatment of concomitant chronic heart failure and diabetes mellitus by regulating the activity of the H19/miR-423-5p/HCN4 axis

IntroductionIn this study, the molecular mechanisms underlying the therapeutic effect of metformin (MET) and ivabradine (IBD) in the treatment of concomitant chronic heart failure (CHF) and diabetes mellitus (DM) were investigated.Material and methodsBasic and cardiac indexes were measured to study the therapeutic effect of MET and IBD. Real-time PCR, IHC assays, in-silicon analysis, luciferase assays, real-time PCR and Western blot assays were conducted to clarify the molecular mechanisms underlying the interaction between MET and IBD.ResultsMET administration restored the normal values of general/cardiac indexes in CHF rats. The abnormal values of echocardiographic indexes in CHF rats with STZ-induced DM were all corrected by a certain degree after the MET administration. Moreover, the injection of STZ up-regulated the expression of plasma NE/BNP-45, while the IBD administration reduced the levels of NE/BNP-45 in CHF rats. Furthermore, the administration of MET also reduced the NE level in CHF rats, indicating that both MET and IBD can exert a therapeutic effect on CHF rats. Additionally, in-silicon analysis and luciferase assays verified the role of H19 and HCN4 as target genes of miR-423-5p. In fact, the transfection of MET or H19 siRNA1/2 into HL-1 and H9C2 cells down-regulated the levels of H19 and HCN4 while increasing the level of miR-423-5p.ConclusionsMET reduces H19 expression via inducing methylation of its promoter, and the inhibited H19 expression suppresses HCN4 expression by up-regulating miR-423-5p expression. As a result, the suppressed expression of HCN4 reduces heart rate and exhibits a therapeutic effect in the treatment of concomitant CHF and DM.

Effects of canagliflozin in patients with type 2 diabetes and chronic heart failure: a randomized trial (CANDLE)

Abstract Background Little is known about the impacts of sodium glucose co-transporter 2 inhibitors on cardiac functional parameters, such as natriuretic peptides, in type 2 diabetes (T2D) patients with concomitant chronic heart failure (CHF). Purpose To compare the effect of canagliflozin with glimepiride, based on changes in N-terminal pro-brain natriuretic peptide (NT-proBNP), in that patient population. Methods This trial was an investigator-initiated, multicenter, prospective, randomized, open-label, blinded-endpoint trial at 34 centers in Japan. Patients with T2D and clinically stable CHF excluding NYHA class IV, randomized to receive canagliflozin 100 mg or glimepiride (starting dose: 0.5 mg), were examined using the primary endpoint of non-inferiority of canagliflozin versus glimepiride, defined as a margin of 1.1 in the upper-limit of the 2-sided 95% confidence interval (95% CI) for the group ratio of percentage change in NT-proBNP at 24 weeks. Results Data analysis of 233 patients (mean age 68.6±10.1 yrs; 75% male) showed mean left ventricular ejection fraction (LVEF) at randomization was 57.6±14.6%, with 71% of patients having a preserved LVEF (≥50%). The ratio of NT-proBNP percentage change was 0.48 (95% CI, −0.13 to 1.59, P=0.226), and therefore did not meet the prespecified non-inferiority margin. However, data stratified according to baseline NT-proBNP levels showed a trend that canagliflozin treatment reduced NT-proBNP levels to a greater extent than in subgroups with elevated levels of NT-proBNP (Figure A). Furthermore, NT-proBNP levels in the canagliflozin group did show a nonsignificant trend lower in the subgroup with preserved LVEF (Figure B), but not in the subgroup with reduced LVEF (Figure C). Additionally, the changes in the NYHA class were comparable between groups (P=0.061) in the overall cohort, whereas in the subgroup with a preserved LVEF canagliflozin caused a significant improvement in NYHA classes compared to that found for glimepiride treatment (P=0.027). Conclusions This trial did not meet the predefined primary endpoint of changes in NT-proBNP levels, with 24 weeks of treatment with canagliflozin relative to glimepiride which together with other recent studies would question the value of continuing to monitor NT-proBNP levels after the initial diagnosis of heart failure. Nevertheless, in a subgroup with preserved LVEF, there was a non-significant trend for canagliflozin treatment to reduce NT-proBNP levels and improve symptoms even in stable HF patients. Further research is therefore warranted to determine whether patients with preserved LVEF, regardless of diabetes status, could potentially benefit from treatment with SGLT2 inhibitors. Changes in NT-proBNP Funding Acknowledgement Type of funding source: Private company. Main funding source(s): Mitsubishi Tanabe Pharma Corporation

Effects of canagliflozin in patients with type 2 diabetes and chronic heart failure: a randomized trial (CANDLE).

AimsLittle is known about the impact of sodium glucose co‐transporter 2 (SGLT2) inhibitors on cardiac biomarkers, such as natriuretic peptides, in type 2 diabetes (T2D) patients with concomitant chronic heart failure (CHF). We compared the effect of canagliflozin with glimepiride, based on changes in N‐terminal pro‐brain natriuretic peptide (NT‐proBNP), in that patient population.Methods and resultsPatients with T2D and stable CHF, randomized to receive canagliflozin 100 mg or glimepiride (starting‐dose: 0.5 mg), were examined using the primary endpoint of non‐inferiority of canagliflozin vs. glimepiride, defined as a margin of 1.1 in the upper limit of the two‐sided 95% confidence interval (CI) for the group ratio of percentage change in NT‐proBNP at 24 weeks. Data analysis of 233 patients showed mean left ventricular ejection fraction (LVEF) at randomization was 57.6 ± 14.6%, with 71% of patients having a preserved LVEF (≥50%). Ratio of NT‐proBNP percentage change was 0.48 (95% CI, −0.13 to 1.59, P = 0.226) and therefore did not meet the prespecified non‐inferiority margin. However, NT‐proBNP levels did show a non‐significant trend lower in the canagliflozin group [adjusted group difference; −74.7 pg/mL (95% CI, −159.3 to 10.9), P = 0.087] and also in the subgroup with preserved LVEF [−58.3 (95% CI, −127.6 to 11.0, P = 0.098]).ConclusionsThis study did not meet the predefined primary endpoint of changes in NT‐proBNP levels, with 24 weeks of treatment with canagliflozin vs. glimepiride. Further research is warranted to determine whether patients with heart failure with preserved ejection fraction, regardless of diabetes status, could potentially benefit from treatment with SGLT2 inhibitors.

Особливості клінічного перебігу негоспітальної пневмонії у хворих із супутньою хронічною серцевою недостатністю

SummaryThe purpose of the work is to determine the features of the clinic, diagnosis and course ofcommunity-acquired pneumonia (P) in patients with chronic heart failure (CHF).Material and methods. 88 patients with P were examined, the average age of whichwas (61.3±2.2) years, who were admitted and examined at the pulmonology clinic ofNational Military Medical Clinical Center «The Main Military Clinical Hospital» of theMinistry of Defense of Ukraine. The main group included 45 persons with P and CHF,and the comparison group – 43 persons with P without signs of CHF, matched by ageand sex. In order to determine the place of treatment and the development of adverseeffects of P for all patients, a disease severity index on the PORT (PSI) and CRB-65scales was calculated.Results and discussion. In the main group of patients, a significantly higher body massindex was observed, in the majority of cases compensated or subcompensated type 2 diabetesmellitus, chronic kidney disease of I–II study were found as well as a significantly higherpercentage of persons, who have been taking antibacterial drugs for the past three months. Inthe main group of patients there were no patients with grade 1–2 risk of adverse pneumonia,because all patients had two or more comorbidities. It was found that there were significantly among those who had a severe course of P in the main group with multiple concomitantpathology of two or more systems. According to the results of X-ray chest examination, a -significantly higher percentage of patients with bilateral lesions (35.6%, p<0.05) and multiplesection pneumonic infiltration (22.2%, p<0.05) were found in patients of the main group. At thesame time, the comparison group was characterised by domination of patients with unilateralpneumonic infiltration (62.8%, p<0.05).Conclusions. It was found that the clinical course of P in patients with CHF has ahigher score for risk of death from P by the PSI pneumonia severity scale (r=0.635,p<0.05). Patients with P with concomitant CHF were found to have a higher percentageof severe cases with bilateral (35.6%) or multiple partial lung lesions (22.2%).

Acute decompensated heart failure increases the anticoagulation effect of dabigatran: A case report

Dabigatran is a widely used non-Vitamin K antagonist oral anticoagulant and has demonstrated a better efficacy and safety profile compared to Vitamin K antagonists. However, in some specific situations, the bleeding risk of dabigatran will be much increased. A 76-year-old female atrial fibrillation patient with concomitant nonrheumatic mitral valve regurgitation and chronic heart failure was described. She was on dabigatran 110 mg twice a day. On day 2 after admission, the patient presented with acute decompensated heart failure, the creatinine clearance level markedly decreased from 40.9 mL/min to 23.1 mL/min, and the trough-activated partial thromboplastin time exceeded the detection range. In this clinical context, renal and coagulation function should be monitored closely to avoid severe adverse events, especially major bleeding. Low-molecular-weight heparin might be considered to be applied temporarily, and rivaroxaban may be prescribed in this condition. The ethical approval was waived by the institutional review board of our hospital owing to the retrospective nature of the study.

P4564Sympathetic renal denervation in patients with refractory arterial hypertension: 2-years follow-up

Abstract Aim To evaluate the efficacy of the sympathetic renal denervation procedure in patients with refractory arterial hypertension and heart failure. Methods The study included 72 patients with refractory arterial hypertension. We used randomization in 2 main groups: the Group I (n=36) included patients, who underwent denervation procedure of the main trunk of the renal artery and the Group 2 (n=36) - included patients who underwent denervation procedure in main trunk and also in second-order renal arteries. Additionally, patients were divided into 2 subgroups: the subgroup A (n=30) included patients, who underwent denervation procedure with a SYMPLICITY catheter, and the subgroup B (n=42) - included patients who underwent denervation procedure with a VESSIX catheter. Also, the renal denervation procedure efficacy, in patients with chronic heart failure (CHF) was analyzed. In all groups, 24-hour blood pressure monitoring, echocardiography and a 6-minute walk test were monitored. Inclusion criteria: refractory hypertension, age of patients 18–85 years, systolic blood pressure (SBP) ≥140/90 mmHg and ≥130/90 mmHg in patients with diabetes mellitus, functioning kidneys, renal arteries ≥40 mm in diameter and the length of the site up to the first bifurcation of at least 20 mm, absence of stenoses in the renal arteries, GFR≥40 ml/min/1.73m2, suitable anatomy of the renal arteries for endovascular procedure. Results 24 months result after the denervation procedure was demonstrated significantly decreased SBP in patients of both groups. In group I, it was, compared with pre-operative data (174.9±1.6 vs. 151.7±2.3 mmHg, respectively; p&lt;0.05), and in group II - 181.9±2.1 vs. 140.4±3.8 mmHg, respectively; p&lt;0.05). However, when comparing SBP values between groups, SBP in group I was significantly higher, than in group II (151.7±2.3 vs. 140.4±3.8 mmHg, respectively; p&lt;0.05). In addition, the average number of drugs in group I was decreased to 2.1±0.8 after 24th month, and in group II - to 1.4±0.6 (p&lt;0.05). When comparing SBP value in subgroup A and subgroup B, the average daily SBP also significantly difference and amounted to 147.8±1.8 vs. 138.4±3.2 mmHg, respectively; p&lt;0.05). Among the all patients included in the study, 38 patients were with CHF. The 6-minute walk test results, compared with pre-operative data, showed a significant improvement and amounted to 321.24±83.22 vs. 212.42±54.72m, respectively; p&lt;0.05. Conclusions The sympathetic renal denervation may be regarded as an effective method of treatment of patients with resistant hypertension, as well as patients with concomitant chronic heart failure. Performing denervation in the arteries of the second order, significantly improves the prognosis of patients, and in patients with concomitant heart failure significantly increases the quality of life and exercise tolerance. Acknowledgement/Funding Russian Academic Excellence Project 5-100

Etiology of community-acquired pneumonia in patients with chronic heart failure

Chronic heart failure (CHF) is one of the most common comorbidities in elderly patients with community-acquired pneumonia (CAP).The aim of this study was to investigate etiology of CAP in patients with concomitant CHF.Methods. This prospective observational study involved adult hospitalized patients with CAP and concomitant CHF. CAP was confirmed by chest X-ray. Sputum samples or oropharyngeal swabs, blood and urine samples were collected in all eligible patients before starting the therapy with systemic antibiotics. Sputum was cultured for «typical» bacterial pathogens, such as Streptococcus pneumoniae, Staphylococcus aureus, Enterobacterales, etc., in accordance with standard methods and procedures. Mycoplasma pneumoniae, Chlamydophila pneumoniae and respiratory viruses in sputum or oropharyngeal swabs were identified using the real-time polymerase chain reaction (PCR). Urine samples were used to determine serogroup 1 Legionella pneumophila and S. pneumoniae soluble antigens using bedside immunochromatography.Results. Fifty patients were enrolled in the study. The mean age was 72.2 ± 9.5 years, 27 (54%) were females. The etiology of CAP was identified in 23 cases (46%). S. pneumoniae was the most common pathogen (16/23; 69.7%) followed by respiratory viruses (3/23; 13.1%), such as type 3 parainfluenza virus, coronavirus, human metapneumovirus; Haemophilus influenzae (1/23; 4.3%), S. aureus (1/23; 4.3%), and Klebsiella pneumoniae (1/23; 4.3%). S. pneumoniae and parainfluenza virus co-infection was diagnosed in one of 23 patients (4.3%).Conclusion. S. pneumoniae and respiratory viruses were predominant causative pathogens of CAP in hospitalized adults with concomitant CHF. Therefore, bedside tests for urine pneumococcal antigens should be used more widely considering difficult sputum expectoration in elderly. Atypical bacterial pathogens (M. pneumoniae, C. pneumoniae, L. pneumophila) were not identified in this study, so the routine PCR-test and urine tests for L. pneumophila antigens are thought to be not useful.

Proteomic analysis in the diagnostics of chronic heart failure with normal ejection fraction

This review is devoted to the analysis of information on protein-markers of chronic heart failure (CHF). The review contains current information about protein predictors of cardiovascular disease and concomitant CHF. The methodology of proteomic analysis is considered. The following conclusions were made: 1. The method of controlling the expression of individual genome sections proteomic analysis is a method of early, preclinical diagnosis of diseases, because it allows to identify the initial stages of the pathological genome in the phenotype. 2. The study of CHF protein markers is at the primary stage of accumulation of factual material, making this research direction promising. 3. In many ways, in addition to the prognostic effect of pathological protein-markers, the detection allows to understand the pathogenesis of the disease, its implementation at the molecular level. 4. In turn, determining exact molecular mechanisms of the pathological process development helps finding new treatment modalities. 5. Changes in the number of pathological protein-markers dynamics allows to predict the severity and outcome of the disease.

C-reactive protein evaluation in communityacquired pneumonia with comorbid chronic heart failure as criterion of antibiotic prescription

To prove that diagnostic algorithm based on additional measurement of serum C-reactive protein (CRP) for administration of systemic antibacterial therapy (ABT) to patients with suspected community-acquired pneumonia (CAP) and concomitant chronic heart failure (CHF) does not influence outcomes of disease. This open, single-center, randomized, prospective, noninferiority study included 160 adult patients with documented functional class II-IV CHF who had been admitted with a preliminary diagnosis of non-severe CAP. Patients were randomized at 1:1 to two groups; group 1 - with additional measurement of CRP (n=80) and group 2 - with the use of routine diagnostic methods (n=80). In group 1, systemic ABT was administered only when serum CRP was &gt;28.5 mg / l (threshold level of the biomarker calculated at the previous stage of the study); group 2 received a standard treatment. Noninferiority test result for both algorithms was evaluated by the number of patients with clinical success on days 12-14 (primary endpoint). Non-inferiority margin was δ=-13.5 %. In addition secondary endpoints (early clinical response on days 3-5; early in-hospital adverse events (development of complications; admission to intensive care unit (ICU); death), death, recurrent CAP or CHF worsening with readmission at 28 day; mortality at 90 and 180 days) were estimated. Standard statistical tools were used for all intergroup comparisons. 76 patients of each group reached the primary endpoint. Systemic ABT was administered to 51 (67.1 %) patients in group 1 and 76 (100 %) patients in group 2 (p&lt;0.05). Both groups were comparable (p&gt;0.05) regarding all endpoints: clinical success, 70 (92.1 %) vs. 69 (90.8 %), Δ=1.3 % (one-sided 97.5 % CI: - 8.25 % for non-inferiority margin δ=-13.5 %); early clinical response, 66 (86.8 %) vs. 68 (89.5 %); admission to ICU, 1 (1.3 %) vs. 1 (1.3 %); development of complications, 20 (26.3 %) vs. 22 (28.9 %); readmission, 5 (6.6 %) vs. 6 (7.9 %); in-hospital mortality, 2 (2.6 %) vs. 1 (1.3 %), mortality at 28 day, 3 (3.9 %) vs. 2 (2.6 %), at 90 day, 5 (6.6 %) vs. 4 (5.3 %), at 180 day, 8 (10.5 %) vs. 9 (11.8 %) cases, respectively. additional measurement of serum CRP in patients with CHF and suspected non-severe CAP was able to reduce rate of systemic ABT administration without outcomes and prognosis worsening.